Diabetes and thyroid disorders in clinical practice today

Transcription

1 St Petersburg, Russia - April 25, 2015 Diabetes and thyroid disorders in clinical practice today IMPROVING THE PATIENT S LIFE THROUGH MEDICAL EDUCATION

2 Paolo Pozzilli Dept. Endocrinology and Diabetes, University Campus Bio-Medico of Rome, Italy Centre of Diabetes, St. Bartholomew's and The London School of Medicine Queen Mary University of London, UK Declared receipt of grants and contracts; honoraria or consultation fees.

3 St Petersburg, Russia - April 25, 2015 Type 2 diabetes, metabolic syndrome and thyroid diseases IMPROVING THE PATIENT S LIFE THROUGH MEDICAL EDUCATION

4 Highlights in Type 2 diabetes Metabolic syndrome Thyroid diseases

5 Obesity Trends* Among U.S. Adults BRFSS, 1991 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19%

6 Obesity Trends* Among U.S. Adults BRFSS, 1992 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19%

7 Obesity Trends* Among U.S. Adults BRFSS, 1993 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19%

8 Obesity Trends* Among U.S. Adults BRFSS, 1994 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19%

9 Obesity Trends* Among U.S. Adults BRFSS, 1995 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19%

10 Obesity Trends* Among U.S. Adults BRFSS, 1996 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19%

11 Obesity Trends* Among U.S. Adults BRFSS, 1997 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20%

12 Obesity Trends* Among U.S. Adults BRFSS, 1998 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20%

13 Obesity Trends* Among U.S. Adults BRFSS, 1999 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20%

14 Obesity Trends* Among U.S. Adults BRFSS, 2000 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20%

15 Obesity Trends* Among U.S. Adults BRFSS, 2001 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14 15% 19% 20% 24% 25%

16 Obesity Trends* Among U.S. Adults BRFSS, 2002 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14 15% 19% 20% 24% 25%

17 Obesity Trends* Among U.S. Adults BRFSS, 2003 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14 15% 19% 20% 24% 25%

18 Obesity Trends* Among U.S. Adults BRFSS, 2004 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14 15% 19% 20% 24% 25%

19 Obesity Trends* Among U.S. Adults BRFSS, 2005 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

20 Obesity Trends* Among U.S. Adults BRFSS, 2006 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

21 Obesity Trends* Among U.S. Adults BRFSS, 2007 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

22 Obesity Trends* Among U.S. Adults BRFSS, 2008 (*BMI 30, or ~ 30 lbs. overweight for 5 4 person) No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

23 Prevalence of Self-Reported Obesity Among Non- Hispanic White Adults,by State, BRFSS, % Data not reported* 15% <20% 20% <25% 25% <30% 30% <35% * Sample size <50 or the relative standard error (dividing the standard error by the prevalence) 30%.

24 Prevalence of Self-Reported Obesity Among Hispanic A by State, BRFSS, % Data not reported* 15% <20% 20% <25% 25% <30% 30% <35% * Sample size <50 or the relative standard error (dividing the standard error by the prevalence) 30%.

25 Prevalence of Self-Reported Obesity Among Non-Hispa Black Adults, by State, BRFSS, % Data not reported* 15% <20% 20% <25% 25% <30% 30% <35% * Sample size <50 or the relative standard error (dividing the standard error by the prevalence) 30%.

26 Factor structure of the metabolic syndrom Insulin Resistance Fasting Insulin Fasting Glucose Obesity Body Mass Index Waist/Hip Ratio Lipids HDL Cholesterol Triglycerides Blood pressure Systolic BP Diastolic BP Adapted from Shen et al. Am J Epidemiol, 157: , 2003

27 Genetic factors Tessuto Visceral adiposo sottocutaneo adipose tissue FFA TNF- PAI-1 ILs Insulin resistance Environmental factors Glucose uptake Gluconeogenesis VLDL syntesis Hypertriglyceridemia Hyperglycemia Hyperinsulinemia

28 Insulin resistance Adipose tissue FFA

29 Relationship between visceral fat and insulin sensitivity Total glucose (mmol/min/kg FFM) Bonora E et al, Ital Cardiol, r = p< Visceral fat amount (cm 2 )

30 The variability of waist circumference Fox K et al., Int J Obes Relat Metab Disord, 1993 Waist circumference is subject to interoperator variability and is influenced by: 1) gender; 2) race or ethnicity Waist circumference explains only 25% to 50% of the variation in intra-abdominal adipose tissue.

31 The study findings suggest a close relationship among wrist circumference, its bone component, and insulin resistance in overweight/obese children and adolescents, opening new perspectives in the prediction of cardiovascular disease. Buzzetti R. et al., Circulation, 2011

32 Wrist circumference as a predictor of T2D Incidence of diabetes during 8.8 years of follow-up ( Noudeh et al. JCEM 2013)

33 Type 2 diabetes and personalized therapy

34 T2DM is a COMPLEX disease with a COMPLEX therapy! Detemir Glargine Degludec U 300 Lispro Aspart Glulisine Regular human Biosimilar insulin INSULIN Glicazide Glibenclamide Glimepiride Glyburide SULFONYLUREAS Pioglitazone TZDs Nateglinide Repaglinide Metformin GLINIDES BIGUANIDES Sitagliptin Saxagliptin Vildagliptin Linagliptin Alogliptin DPP-IV INHIBITORS Exenatide Exenatide LAR Liraglutide Lixisenatide Dulaglutide LAR Albiglutide LAR Senaglutide INCRETINS Acarbose Miglitol ALPHA GLUCOSIDASES INHIBITORS Dapagliflozin Ertugliflozin Canagliflozin Empagliflozin Sotagliflozin SGLT2 INHIBITORS

35 DPP-4I and cardiovascular outcomes NCT (n= 5.000) CARMELINA (n estimated=8.300) CAROLINA (n estimated=6.000) SAVOR TIMI 53 (n=18.206) EXAMINE (n= 5.380) TECOS (n=14.000) Clinicaltrials.gov

36 GLP-1A and cardiovascular outcomes SUSTAIN 6 (n=3.297) REWIND (n estimated=9.622) ELIXA (n=6.075) EXSCEL (n estimated= ) LEADER (n=9.340) Clinicaltrials.gov

37 SGLT-2 and cardiovascular outcomes MK (n estimated=3.900) EMPA REG (n= 7.000) DECLARE TIMI (n estimated=17.150) CANVAS (n estimated= 4.365) Clinicaltrials.gov

38 The A1C and ABCD(E)* of glycaemia management in type 2 diabetes: a physician's personalized approach AGE (years) >70 COMPLICATIONS DURATION>10yrs HbA1c (%) <6 <6.5 < <7 7-8 HbA1c 9% Insulin treatment HbA1c< 9% METFORMIN Physicia n should choose drug a ccording to pa tie nt's risk of w e ight ga in, hypoglyca e mia, ca rdio-re na l complica tions Pozzilli P, Leslie RD, Chan J, De Fronzo R, Monnier L, Raz I, Del Prato S. Diabetes Metab Res Rev May;26(4): *Khazrai YM, Buzzetti R, Del Prato S, Cahn A, Raz I, Pozzilli P. J Diabetes Complications Mar 11. pii: S1056-

39 ADA/EASD position statement 2015 Towards personalized glycaemic targets Diabetes Care, Volume 38, supplement 1, January 2015

40 Maddaloni E.& Pozzilli P. Endocrine, January 2014 The «SMART» diabetologist afety Primum non nocere The challenge for diabetologist is to choose the best safe approach with concerns to potential adverse effects and benefits of intensive glucose control. ultifactorial pproach isk herapy In diabetic patients relevant cardiovascular risk factors other than hyperglycaemia always coexist. There is a universal agreement that anti-hyperglycaemic therapy should be pursued within a multifactorial risk reduction framework A careful evaluation of the risk reduction that could really be achieved should always be performed. However the risk of macrovascular complications starts to increase very early, even in the pre-diabetic stages, claiming for precocious management strategies. Therapy of diabetes is becoming increasingly complex, due to the complexity of pathophysiology and to the wide therapeutic options. A non univocal, but just a smart approach could be the key to turn therapeutic complexity from a problem into an opportunity.

41 complex human behaviour It is important that patients learn to manage and cope with their disease and gain greater control over actions and decisions affecting their health. Healthcare professionals should aim to encourage and increase patients perception about their ability to take informed decisions about disease management and to improve patient self-esteem and feeling of self-efficacy to become agents of their own health. Khazrai YM et al., JDC 2015

42 A ge B ody weight C omplications D uration of disease E mpowerment / economics Patient perspective Normal glycaemia Easy to use Safe and tolerable Immediate benefit Inexpensive Physician perspective Durability Easy to prescribe Reduce complications Long-term benefit Preserve beta-cells

43 Considerations for personalizing medicine in T2DM therapy Efficacy Cost Age Safety and tolerability Personalized Therapy Occupation Patient wishes Diabetes Duration Concomitant Diseases Body Weight The A1C and ABCD of glycaemia management in type 2 diabetes: a physician's personalized approach. Pozzilli P, Leslie RDG, Chan J, De Fronzo R, Monnier L, Raz I, Del Prato S: Diabetes Metab Res Rev 26:239-44, 2010

44 Thyroid and other diseases associated with diabetes

45 Prevalence of autoimmune thyroid and other diseases associated with type 1 diabetes Barker JM et al, JCEM, 2011; Hollowell JC, JCEM, 2012; Van den Driessche et al, J Med, 2009; Bowes J, Rheumat, 2008 T1DM (%) General population (%) Coeliac disease Hashimoto 3-8 <1 Graves disease 1 1 Addison disease < Autoimmune gastritis Pernicious anemia Multiple sclerosis Vitiligo Rheumatoid Arthritis Systemic Lupus Erithematosus

46 Prevalence autoantibodies in type 1 diabetes and in general population Barker JM et al, JCEM, 2006; Alonso N et al, Nat Rev, 2009 Autoantigen T1DM (%) General population (%) Celiac disease ttg Hashimoto TPO TG Graves'disease TRAb 5 1 Addison disease 21-OH 1-2 Rare Autoimmune gastritis APCA

47 Prevalence of organ-specific autoantibodies in NIRAD /LADA and T2D patients High titre GADA p<0.001 p<0.004 Low titre GADA T2DM p<0.03 p< p= TPO 21-OH ttg APC Zampetti S et al., J Clin Endocrinol Metab 97: , 2012

48 Conclusions Interaction between obesity, diabetes and autoimmune thyroid and other diseases is more than an association of different conditions but a pathophysiological cluster which requires precise characterization for the implementation of the most suitable therapy.

49 St Petersburg, Russia - April 25, 2015 Diabetes and thyroid disorders in clinical practice today IMPROVING THE PATIENT S LIFE THROUGH MEDICAL EDUCATION